Clinical studies have linked the experience of stressful events, such as pressure, cancer-related concerns and depression, to poor survival of cancer patients [
1,
2]. Preclinical studies also support that chronic stress has an impact on cancer progression and survival [
3‐
5]. Glucocorticoids (GCs) are main stress hormones which are secreted dramatically in a state of stress, and play a critical role in the process of immunosuppression, anti-inflammation and homeostasis sustaining [
6]. Synthetic GCs, such as dexamethasone, have been widely used as drugs to treat immune and inflammatory disorders. Moreover, GCs are clinically important as adjuvants in non-hematologic cancer therapy to reduce acute toxicity and alleviate side effects induced by chemotherapy or radiotherapy [
7]. GCs exert their biological effects by regulating the expression of genes and cross-talking with multiple trans-membrane signalling pathways [
8]. The effects of GCs are mediated by glucocorticoid receptor (GR), which is ubiquitously expressed in all cells. Since the activation of GR by GCs control a variety of physiological and cellular processes, such as immune response, metabolism, cell proliferation, apoptosis and survival [
9], the relationship between GCs and solid tumors has been concerned. Although there are reports that GCs have the inhibitory effect on proliferation and progression in several tumors in vitro and in vivo [
10‐
13], other and our studies have demonstrated that GCs induce resistance to chemotherapy in the majority of solid tumor cells [
14‐
16], promote metastasis of pancreatic cancer [
17] and melanoma cells [
18], and increase risks of skin cancer and non-Hodgkin’s lymphoma [
19]. It still remains unclear whether these controversial phenomena are attributed to the dose and duration of GC treatment, as well as cell and tissue specific GC signal transduction. Therefore, it is vital to further evaluate the role of GCs in carcinogenesis and progression of different solid tumors, especially in vivo.
Colorectal carcinoma (CRC) is one of the top three diagnosed cancers worldwide. It can develop spontaneously or as a complication of inflammatory bowel diseases. It is believed that chronic inflammation increase the risk of CRC development [
20]. Limited studies about the effect of GCs on growth of CRC have been done in vitro and in vivo, and the results are not concordant. Inhibitory effect or promoting effect that GCs showed on growth of CRC depended on cell lines [
21‐
23], tumor micro-environment [
24,
25] and the delivery formulation and dosage of GCs [
26]. In addition, previous animal studies were done using the xenografts model mice which are featured by immunodeficiency, while the result from these mice is not equal to that of intact mice with induced carcinoma in colorectum spontaneously. A mouse CRC model induced by azoxymethane and dextran sulfate sodium (AOM/DSS) is a stable and reliable model of spontaneous tumor and has been used in CRC studies [
27‐
29]. AOM is a chemical mutagen, which induces colonic tumor with clinical, histological and molecular features of human sporadic colon cancer, and the follow-up treatment with the non-genotoxic DSS strongly induces inflammation in the colon, thereby enhancing the colon carcinogenesis in rodents [
30]. In this study, we investigated whether corticosterone (CORT), a major form of GCs in mouse, influenced the development of CRC in such a mouse model of colorectal carcinogenesis induced by AOM/DSS.